OBJECTIVES: I. Determine the optimum dose of tauroursodeoxycholic acid (TUDCA) required to achieve maximal bioavailability for patients with cystic fibrosis-associated liver disease. II. Compare optimized doses of TUDCA with ursodiol (ursodeoxycholic acid; UDCA) for effects on biliary bile acid composition and metabolism, serum biochemistries, fat absorption, and fat-soluble vitamin status in these patients.

Condition	Treatment or Intervention
Cystic Fibrosis	Drug: tauroursodeoxycholic acid  Drug: ursodiol

Further Study Details: 

Expected Total Enrollment:  39

PROTOCOL OUTLINE: Objective I: This part of the study is a dose-response study to determine the optimal dose of tauroursodeoxycholic acid (TUDCA). Twenty-four patients are randomized to receive one of three different doses of TUDCA for 3 months. Objective II: This part of the study is a double-blind crossover study to compare optimized doses of TUDCA with optimized doses of ursodiol in 15 patients stratified according to age (less than 10 vs 10-20 vs more than 20 years). Patients are randomized to receive either TUDCA or ursodiol orally for an initial 3 month period, followed by a 3 month washout period in which no drug is administered. Patients then receive the alternate drug for 3 months.

Genders Eligible for Study:  Both

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Cystic fibrosis-associated liver disease, defined by at least one of the following criteria: (1) Documented increase in serum concentrations of any of the liver enzymes (at least once in the preceding year) ALT at least twice normal AST at least 1.5 times normal Alkaline phosphatase at least 1.5 times normal GGT at least 1.5 times normal (2) Persistent hepatomegaly of more than 6 months duration defined by percussed liver span greater than 1 SEM for age (3) Splenomegaly, defined as a palpable spleen greater than 2.0 cm below the left costal margin (4) Abnormalities of ultrasound scan (increased size, dishomogeneous echogenicity, nodular liver, irregular margins, splenomegaly) within 6 months prior to study entry
• Patients enrolled in the first part of the study (objective I) are eligible to participate in the second part (objective II)

--Prior/Concurrent Therapy--

• At least 3 months since prior ursodiol
• At least 3 months since treatment with drug with choleretic properties or effects that influence bile acid metabolism

--Patient Characteristics--

• Hepatic: No decompensated cirrhosis No hepatic neoplasm or cholelithiasis
• Pulmonary: No significantly impaired pulmonary function with FEV1 less than 50%
• Other: At least 15 kg body weight No severely compromised clinical or nutritional state

Colorado
      Children's Hospital of Denver, Denver,  Colorado,  80218,  United States; Recruiting
Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States; Recruiting
Italy
      University of Milan, Milan,  20122,  Italy; Recruiting

Study chairs or principal investigators

Kenneth Setchell,  Study Chair,  Children's Hospital Medical Center - Cincinnati   

Study ID Numbers:  199/13439; CHMC-C-001439; CHMC-C-96-1-8; CHMC-C-FDR001439-01
Record last reviewed:  July 1998
Last Updated:  October 13, 2004
Record first received:  October 18, 1999
ClinicalTrials.gov Identifier:  NCT00004441
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08